A viral vector expressing hypoxia-inducible factor 1 alpha inhibits hippocampal neuronal apoptosis  

作　　者：Xiqing Chai Weina Kong Lingyun Liu Wenguo Yu Zhenqing Zhang Yimin Sun 

机构地区：[1]Bioreactor and Protein Drug Research and Development Center of Hebei Universities, Hebei Chemical and Pharmaceutical College [2]Department of Neurology, Shanghai Yangpu District Central Hospital [3]Department of Neurology, the First Hospital of Hebei Medical University

出　　处：《Neural Regeneration Research》2014年第11期1145-1153,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81273983;the Natural Science Foundation of Hebei Province of China,No.C2010001471;the Scientific Research Fund of Hebei Provincial Education Department in China,No.Q2012036

摘　　要：Hypoxia-inducible factor 1 （HIF-1） attenuates amyloid-beta protein neurotoxicity and decreases apoptosis induced by oxidative stress or hypoxia in cortical neurons. In this study, we construct-ed a recombinant adeno-associated virus （rAAV） vector expressing the human HIF-1αgene （rAAV-HIF-1α）, and tested the assumption that rAAV-HIF-1αrepresses hippocampal neuronal apoptosis induced by amyloid-beta protein. Our results conifrmed that rAAV-HIF-1αsigniifcant-ly reduces apoptosis induced by amyloid-beta protein in primary cultured hippocampal neurons. Direct intracerebral rAAV-HIF-1αadministration also induced robust and prolonged HIF-1αproduction in rat hippocampus. Single rAAV-HIF-1αadministration resulted in decreased apoptosis of hippocampal neurons in an Alzheimer＇s disease rat model established by intrace-rebroventricular injection of aggregated amyloid-beta protein （25-35）. Our in vitro and in vivo ifndings demonstrate that HIF-1 has potential for attenuating hippocampal neuronal apoptosis induced by amyloid-beta protein, and provides experimental support for treatment of neurode-generative diseases using gene therapy.Hypoxia-inducible factor 1 （HIF-1） attenuates amyloid-beta protein neurotoxicity and decreases apoptosis induced by oxidative stress or hypoxia in cortical neurons. In this study, we construct-ed a recombinant adeno-associated virus （rAAV） vector expressing the human HIF-1αgene （rAAV-HIF-1α）, and tested the assumption that rAAV-HIF-1αrepresses hippocampal neuronal apoptosis induced by amyloid-beta protein. Our results conifrmed that rAAV-HIF-1αsigniifcant-ly reduces apoptosis induced by amyloid-beta protein in primary cultured hippocampal neurons. Direct intracerebral rAAV-HIF-1αadministration also induced robust and prolonged HIF-1αproduction in rat hippocampus. Single rAAV-HIF-1αadministration resulted in decreased apoptosis of hippocampal neurons in an Alzheimer＇s disease rat model established by intrace-rebroventricular injection of aggregated amyloid-beta protein （25-35）. Our in vitro and in vivo ifndings demonstrate that HIF-1 has potential for attenuating hippocampal neuronal apoptosis induced by amyloid-beta protein, and provides experimental support for treatment of neurode-generative diseases using gene therapy.

关 键 词：nerve regeneration Alzheimer＇s disease adeno-associated virus hypoxia-inducible fac-tor 1~ apoptosis gene therapy calcium concentration TRANSDUCTION intracerebroventricular injec-tion NSFC grant neural regeneration 

分 类 号：R749.16[医药卫生—神经病学与精神病学]